Wong, Hermon Kha Kin

Abstract Background Recurrence of symptomatic atrial fibrillation (AF) after catheter ablation (CA) is not uncommon. However, real-world long-term data on clinical outcomes of rhythm control strategies in patients with recurrent AF after CA remain limited. Methods Using the TriNetX database, we identified adult patients (≥18 years) with recurrent AF after index CA. A 3-month blanking period was applied, during which no rhythm-control therapy was received. Patients were classified into two groups: repeat CA or initiation of antiarrhythmic drug (AAD) therapy. Propensity score matching (PSM) was performed to balance baseline characteristics. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Outcomes included all-cause mortality, all-cause hospitalization, heart failure (HF) exacerbation, ischemic stroke, and major bleeding over 5 years. Results Among 4,056 patients with recurrent AF post-CA, 17.2% underwent repeat CA. After PSM, 697 patients in the repeat CA group (mean age 68.9 ± 9.6 years; 35.7% female) and 697 in the AAD group (mean age 68.4 ± 10.0 years; 37.6% female) were analyzed. Repeat CA was associated with lower all-cause mortality (3.3% vs 8.2%; HR 0.44; 95% CI, 0.27–0.72; P < 0.01), all-cause hospitalization (42.8% vs 56.4%; HR 0.71; 95% CI, 0.61–0.82; P < 0.01) and HF exacerbation (12.5% vs 24.8%; HR 0.50; 95% CI, 0.39–0.64; P < 0.01). No differences were observed in ischemic stroke (5.3% vs 4.7%; HR 1.22; 95% CI, 0.77–1.96; P = 0.40) or major bleeding (4.6% vs 6.2%; HR 0.82; 95% CI, 0.52–1.29; P = 0.39). Conclusions Repeat CA was associated with lower mortality, hospitalization, and HF exacerbation over 5 years.

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) both being approved for use. Axi-cel was approved for second-line setting based on studies showing improved outcomes compared to high-dose salvage chemoimmunotherapy followed by autologous hematopoietic stem cell transplantation (HSCT). In contrast, tisa-cel did not demonstrate superiority over traditional salvage therapies in the second-line setting. Although both therapies are currently used in clinical practice, real-world comparative data on the safety of axi-cel versus tisa-cel remain limited. This retrospective study aims to compare the one-year outcomes of axi-cel and tisa-cel in patients with R/R DLBCL, offering practical insights into their outcomes outside of clinical trial settings. Methods A retrospective cohort study was conducted using TriNetX, a global federated health research network that provides access to electronic medical records from approximately 132 million patients, primarily in the United States. Adult patients (≥18 years) diagnosed with R/R DLBCL between January 1, 2022, and January 1, 2024, were identified using ICD-10-CM codes. Patients were categorized into two cohorts: those who received axi-cel and those who received tisa-cel. Propensity score matching (1:1) using nearest neighbor matching with a 0.1 pooled standard deviation caliper was performed for demographics, comorbidities, prior stem cell transplantation, and medications. Study outcomes included 1-year rates of all-cause mortality, all-cause hospitalization, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), anemia, neutropenia, thrombocytopenia, heart failure exacerbation, and acute myocardial infarction. Statistical analyses were conducted on the TriNetX platform, with significance set at P<0.05 (two-sided). TriNetX calculates hazard ratios (HRs) and cumulative incidences (CIs) using R survival package version 3.2-3 with the proportional hazard assumption tested using Schoenfeld residuals. This study does not require Institutional Review Board review or informed consent due to the use of de-identified data. Results Our study identified 1,250 patients with R/R DLBCL, including 1,083 patients who received axi-cel and 167 who received tisa-cel. After propensity score matching (PSM), 160 patients were in the axi-cel group (mean age 61.7 ± 11.8 years; 38.8% female; 73.1% White, 8.1% African American) and 160 patients were in the tisa-cel group (mean age 62.3 ± 16.0 years of age; 39.4% female; 75.0% White, 7.5% African American). Axi-cel group had 45% lower risk of all-cause mortality compared to tisa-cel group (HR: 0.55; 95% CI: 0.34–0.87). However, axi-cel group was associated with higher risks of all-cause hospitalization (HR: 1.33; 95% CI: 1.04–1.70), CRS (HR: 2.19; 95% CI: 1.43–3.36), and ICANS (HR: 2.69; 95% CI: 1.42–5.11) compared to tisa-cell group. No significant differences were observed in anemia (HR: 1.18; 95% CI: 0.82–1.72), neutropenia (HR: 1.30; 95% CI: 0.96–1.77), and thrombocytopenia (HR: 0.96; 95% CI: 0.65–1.43) between these two treatment groups. Additionally, there were no significant differences in terms of septic shock (HR: 0.79; 95% CI: 0.42–1.47), pneumonia (HR: 0.64; 95% CI: 0.34–1.21), and heart failure exacerbation (HR: 1.16; 95% CI: 0.76–1.76) between axi-cel group and tisa-cell group. Conclusion This large and multicenter cohort study provides real-world valuable insights into the one-year comparative outcomes of axi-cel and tisa-cel in patients with R/R DLBCL. Our study suggested axi-cel was associated with lower mortality rate, despites its higher rates of all-cause hospitalization, CRS, and ICANS compared to tisa-cell. These findings highlight the importance of close monitoring and supportive care during the first year following CAR-T therapy to optimize patient outcomes. An important limitation of our study is the lack of data on the number of prior lines of therapy, which may have differed between treatment groups and could have influenced clinical outcomes. Future prospective studies with comprehensive clinical data and inclusion of lisocabtagene maraleucel (liso-cel) would be valuable to provide a more complete comparison across currently available CAR T-cell therapies.

Background: Effective risk factor modification, including management of obesity and diabetes mellitus (DM), is essential to mitigating cardiovascular complications after hematopoietic stem cell transplantation (HSCT). Given the growing use of GLP-1 receptor agonists (GLP-1 RAs), large-scale studies are needed to assess their cardiovascular impact in patients undergoing HSCT. Methods: Using the TriNetX network, we identified patients who underwent HSCT and had DM or obesity. Patients were categorized into two cohorts: those who received GLP-1 RAs and those who did not. Outcomes, including all-cause mortality, all-cause hospitalization, acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and heart failure (HF) exacerbation, were assessed at 1 year, 3 years, and 5 years follow-up. Cohorts were propensity score-matched based on medical comorbidities, transplant diagnoses, and conditioning regimens. Results: Of the initial 17,475 patients with HSCT and DM/obesity, 876 (5.0%, 46.0% females, mean age 58.4 +/- 11.3 years old) received GLP-1 RA and 16,599 (95.0%, 40.8% females, mean age 55.6 +/- 14.3 years old) did not. After propensity score matching, 873 patients were divided equally into each cohort (Table). GLP-1 RA was associated with lower odds of all-cause mortality (1-year: odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.38–0.76; p<0.01; 3-year: OR: 0.52; CI: 0.40–0.69; p<0.01; 5-year: OR: 0.44; CI: 0.33–0.58; p<0.01), all-cause hospitalization (1-year: OR: 0.74; CI: 0.61–0.89; p<0.01; 3-year: OR: 0.66; CI: 0.55–0.79; p<0.01; 5-year: OR: 0.72; CI: 0.59–0.87; p<0.01), and HF exacerbation (1-year: OR: 0.65; CI: 0.44–0.96; p=0.03; 3-year: OR: 0.59; CI: 0.43–0.81; p<0.01; 5-year: OR: 0.53; CI: 0.38–0.74; p<0.01), compared to the non–GLP-1 RA group. At 5-year follow-up, GLP-1 RA use was also associated with lower odds of AF (OR: 0.71; CI: 0.53–0.94; p=0.02). No significant differences were noted in AMI or CVA at 1-, 3-, and 5-years of follow-up. Conclusion: After propensity score-matching in this retrospective cohort study, GLP-1 RA use was associated with significantly lower odds of all-cause mortality, all-cause hospitalization, and heart failure exacerbation at 1-, 3-, and 5-year of follow-up in patients with DM/obesity who underwent HSCT. At 5 years, use of GLP-1 RA was associated with lower odds of AF.

ABSTRACTBackgroundChimeric Antigen Receptor (CAR) T‐cell therapy has arisen as a revolutionary treatment for hematologic malignancies. Our study aimed to evaluate how sex differences affect outcomes and complications following CAR T‐cell therapy.MethodsUtilizing the Nationwide Readmissions Database (2018–2020), we identified patients and divided them into male and female groups. Hospital outcomes and complications were compared among these two groups after propensity score matching to match groups based on comorbidities, producing two comparable cohorts.ResultsWe analyzed 2928 patients (1832 males, 62.6%, mean age 60.3 ± 13.7 years; 1096 females, 37.4%, mean age 59.1 ± 13.8 years). After propensity score matching (1:1ratio), 1092 males and females were compared. There were no significant sex differences in early mortality (adjusted odd ratios (aOR): 1.04 [95% CI 0.69–1.57]), 30‐day readmissions (aOR: 1.05 [95% CI 0.86–1.30]), or nonhome discharge (aOR: 0.89 [95% CI 0.60–1.31]). Females had higher odds of leukopenia (aOR: 1.26 [95% CI 1.06–1.50]) but lower odds of acute kidney injury (aOR: 0.68 [95% CI 0.52–0.88]).ConclusionsNo sex differences were found in hospital outcomes, including early mortality, 30‐day readmission, and nonhome discharge after CAR T‐cell therapy.